Mass spectrometry is an analytical methodology used for qualitative and quantitative chemical analysis of material and mixtures of materials. An analyte, usually an organic, inorganic, biomolecular or biological sample, is broken into electrically charged particles of its constituent parts in an ion source. Next, the analyte particles are separated by the spectrometer based on their respective mass-to-Charge ratios. The separated particles are then detected and a mass spectrum of the material is produced. The mass spectrum is analogous to a fingerprint of the sample material being analyzed by providing information about the masses and quantities of various analyte ions that make up the sample. Mass spectrometry can be used, for example, to determine the molecular weights of molecules and molecular fragments within an analyte. In addition, mass spectrometry can be used to identify molecular structures, sub-structures, and components of the analyte based on the fragmentation pattern, which occurs, when the analyte is broken into particles. Mass spectrometry is an effective analytic tool in chemistry, biology, material science, and a number of related fields.
Many challenges remain in building a mass spectrometer having high sensitivity, high resolution, high mass accuracy, and efficient sample use. One challenge is to efficiently maximize the ionization of a sample as well as allow a dynamic range of analyte samples to be used.
Problems have occurred with various ionization methods creating identifiable differences in mass spectra. For example, the introduction of various solution chemistries during the use of Liquid Chromatography/Mass Spectrometry (LC/MS) can cause notable differences in the mass spectra because one or more ions can exist simultaneously in the mass spectrometer source. During electrospray, the liquid is introduced through a metal capillary which carries an extremely high voltage. This environment creates an electrochemistry cell since the resulting spray or plume or jet is a result of the liquid exceeding its rayleigh limits as it is drawn towards a counterelectrode. Also, the redox reaction occurring during electrospray produces identifiable differences in the mass spectra such as the adduction of metal ions, M+Na. There are several different methods of ionization which have been developed.
Ion sources include methods such as APCI, ESI, and thermospray. Generally, APCI derives ions by heating the liquid flow and creating an aerosol. It is worth noting that APCI does not exhibit such adduction as described above, but will promote background ionization since it ‘uses’ the solvent as a vehicle to transfer charge to the analyte of interest. For example, hydronium ions are created in a plasma through which the analyte travels to become ionized and often tell-tale products such as M+NH4 are created if the liquid contains ammonium acetate. ESI creates the aerosol or plume as a product of the excessive charge. Also related to APCI is thermospray. In general, thermospray is APCI without high voltage (HV) and no APCI needle. (See MDS Parma ASMS poster, 2000). In this method, ions escape the aerosol droplets as they are desolvated.
Of these sources, electrospray sources are amongst the most successful. Although the basic technique of electrospray was known much earlier, the first practical source designs suitable for organic mass spectrometry appeared in 1984 (see e.g., EP 0123552A). Various improvements to this basic electrospray ion source have been proposed. Bruins et ah, (34th Ann. Confr. on Mass Spectrometry and Allied Topics, Cincinnati, 1986, pp 585-6) and (U.S. Pat. No. 4,861,988) describes a pneumatically assisted electrospray source wherein a coaxial nebulizer fed with an inert gas is used in place of the capillary tube of the basic source to assist in the formation of the aerosol. In practice however, sources of this type are often operated with the capillary tube inclined at an angle to the optical axis of the mass analyzer, usually at about 30°, but still directed towards the orifice. U.S. Pat. No. 5,015,845 discloses an additional heated desolvation stage which operates at a pressure of 0.1-10 torr and is located downstream of the first nozzle. While U.S. Pat. Nos. 5,103,093, 4,977,320 and Lee, Henion, Rapid Commun. in Mass Spectrum. 1992, vol. 6 pp. 727-733, and others, teach the use of a heated inlet capillary tube. Furthermore, U.S. Pat. No. 5,171,990 teaches an off-axis alignment of the transfer capillary tube and the nozzle-skimmer system to reduce the number of fast ions and neutrals entering the mass analyzer, and U.S. Pat. No. 5,352,892 discloses a liquid shield arrangement which minimizes the entry of liquid droplets entering the mass analyzer vacuum system.
It has been realized that a major factor in the success of electrospray ionization sources for high-molecular weight samples is that, in contrast with most other ion sources, ionization takes place at atmospheric pressure. Furthermore, ionic and polar compounds ionize by ESI while neutral and weakly-polar compounds typically do not. For this reason, there has been a revival of interest in APCI sources which are also capable of generating stable ions characteristic of high molecular weight, typically <1000 Da, thermally-labile species. Such sources are generally similar to electrospray sources except for the ionization mode.
APCI provides a unique method of ionization by a corona discharge (see Yamashit & Fenn, J Phys Chem., 1984), APCI maintains a corona pin at high potential, allowing the APCI to provide a source of electrons, for example, a beta-emitter, typically a Ni foil, or a corona discharge (see McKeown, Siegel, American Lab. Nov. 1975 pp. 82-99, and Horning, Carroll et al, Adv. in Mass Spectrom. Biochem. Medicine, 1976 vol. 1 pp. 1-16; Carroll, Dzidic et al, Anal. Chem. 1975 vol. 47(14) pp. 2369). In early sources, the high-pressure ionization region was separated from the high vacuum region containing the mass analyzer by a diaphragm containing a very small orifice disposed on the optical axis of the analyzer. Later APCI sources developed into incorporating a nozzle-skimmer separator system in place of the diaphragm (see e.g., Kambara et al., Mass Spectroscopy (Japan) 1976 vol. 24 (3) pp. 229-236 and GB patent application 2183902 A).
Atmospheric pressure ionization sources, in particular electrospray and atmospheric pressure chemical ionization, interfaced with mass spectrometers have become widely used for the analysis of compounds. Ion sources which ionize a sample at atmospheric pressure rather than at high vacuum are particularly successful in producing intact thermally labile high-molecular weight ions.
Previous attempts have been described that create a dual ESI/APCI ionization source. In particular, the dual source ionization relies on a switching box. This modification allows a user to use a control box and two input BNC (bayonet Neill Concelman) connectors of the instrument to either manually or automatically select the voltage for the ESI and APCI modes. Operation of the dual ESI/APCI requires the adjustment of source voltage. Both the ESI and the APCI modes function simultaneously. The most significant parameter controlling the behavior of the source is the temperature and flow rate of the gas (see Seigel et al, J. AM. Soc. Mass Spectrom. 1998, 1196-1203).